Yinming Sun1, Faranak Farzan1, Benoit H Mulsant2, Tarek K Rajji3, Paul B Fitzgerald4, Mera S Barr1, Jonathan Downar5, Willy Wong6, Daniel M Blumberger3, Zafiris J Daskalakis3. 1. Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada. 2. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada. 3. Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada2Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Tor. 4. Monash Alfred Psychiatry Research Centre, Alfred and Monash University Central Clinical School, Victoria, Australia. 5. Department of Psychiatry, University Health Network, University of Toronto, Toronto, Ontario, Canada. 6. Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada.
Abstract
IMPORTANCE: Magnetic seizure therapy (MST) is a novel therapeutic option for treatment-resistant depression (TRD). Suicidal ideation is often associated with TRD and contributes to the increased mortality and morbidity of the disorder. OBJECTIVE: To identify a biomarker that may serve as an indicator of remission of suicidal ideation following a course of MST by using cortical inhibition measures from interleaved transcranial magnetic stimulation and electroencephalography (TMS-EEG). DESIGN, SETTING, AND PARTICIPANTS: Thirty-three patients with TRD were part of an open-label clinical trial of MST treatment. Data from 27 patients (82%) were available for analysis in this study. Baseline TMS-EEG measures were assessed within 1 week before the initiation of MST treatment using the TMS-EEG measures of cortical inhibition (ie, N100 and long-interval cortical inhibition [LICI]) from the left dorsolateral prefrontal cortex and the left motor cortex, with the latter acting as a control site. INTERVENTIONS: The MST treatments were administered under general anesthesia, and a stimulator coil consisting of 2 individual cone-shaped coils was used. MAIN OUTCOMES AND MEASURES: Suicidal ideation was evaluated before initiation and after completion of MST using the Scale for Suicide Ideation (SSI). Measures of cortical inhibition (ie, N100 and LICI) from the left dorsolateral prefrontal cortex were selected. N100 was quantified as the amplitude of the negative peak around 100 milliseconds in the TMS-evoked potential (TEP) after a single TMS pulse. LICI was quantified as the amount of suppression in the double-pulse TEP relative to the single-pulse TEP. RESULTS: Of the 27 patients included in the analyses, 15 (56%) were women; mean (SD) age of the sample was 46.0 (15.3) years. At baseline, patients had a mean SSI score of 9.0 (6.8), with 8 of 27 patients (30%) having a score of 0. After completion of MST, patients had a mean SSI score of 4.2 (6.3) (pre-post treatment mean difference, 4.8 [6.7]; paired t26 = 3.72; P = .001), and 18 of 27 individuals (67%) had a score of 0 for a remission rate of 53%. The N100 and LICI in the frontal cortex-but not in the motor cortex-were indicators of remission of suicidal ideation with 89% accuracy, 90% sensitivity, and 89% specificity (area under the curve, 0.90; P = .003). CONCLUSIONS AND RELEVANCE: These results suggest that cortical inhibition may be used to identify patients with TRD who are most likely to experience remission of suicidal ideation following a course of MST. Stronger inhibitory neurotransmission at baseline may reflect the integrity of transsynaptic networks that are targeted by MST for optimal therapeutic response.
IMPORTANCE: Magnetic seizure therapy (MST) is a novel therapeutic option for treatment-resistant depression (TRD). Suicidal ideation is often associated with TRD and contributes to the increased mortality and morbidity of the disorder. OBJECTIVE: To identify a biomarker that may serve as an indicator of remission of suicidal ideation following a course of MST by using cortical inhibition measures from interleaved transcranial magnetic stimulation and electroencephalography (TMS-EEG). DESIGN, SETTING, AND PARTICIPANTS: Thirty-three patients with TRD were part of an open-label clinical trial of MST treatment. Data from 27 patients (82%) were available for analysis in this study. Baseline TMS-EEG measures were assessed within 1 week before the initiation of MST treatment using the TMS-EEG measures of cortical inhibition (ie, N100 and long-interval cortical inhibition [LICI]) from the left dorsolateral prefrontal cortex and the left motor cortex, with the latter acting as a control site. INTERVENTIONS: The MST treatments were administered under general anesthesia, and a stimulator coil consisting of 2 individual cone-shaped coils was used. MAIN OUTCOMES AND MEASURES: Suicidal ideation was evaluated before initiation and after completion of MST using the Scale for Suicide Ideation (SSI). Measures of cortical inhibition (ie, N100 and LICI) from the left dorsolateral prefrontal cortex were selected. N100 was quantified as the amplitude of the negative peak around 100 milliseconds in the TMS-evoked potential (TEP) after a single TMS pulse. LICI was quantified as the amount of suppression in the double-pulse TEP relative to the single-pulse TEP. RESULTS: Of the 27 patients included in the analyses, 15 (56%) were women; mean (SD) age of the sample was 46.0 (15.3) years. At baseline, patients had a mean SSI score of 9.0 (6.8), with 8 of 27 patients (30%) having a score of 0. After completion of MST, patients had a mean SSI score of 4.2 (6.3) (pre-post treatment mean difference, 4.8 [6.7]; paired t26 = 3.72; P = .001), and 18 of 27 individuals (67%) had a score of 0 for a remission rate of 53%. The N100 and LICI in the frontal cortex-but not in the motor cortex-were indicators of remission of suicidal ideation with 89% accuracy, 90% sensitivity, and 89% specificity (area under the curve, 0.90; P = .003). CONCLUSIONS AND RELEVANCE: These results suggest that cortical inhibition may be used to identify patients with TRD who are most likely to experience remission of suicidal ideation following a course of MST. Stronger inhibitory neurotransmission at baseline may reflect the integrity of transsynaptic networks that are targeted by MST for optimal therapeutic response.
Authors: Bahar Salavati; Tarek K Rajji; Reza Zomorrodi; Daniel M Blumberger; Robert Chen; Bruce G Pollock; Zafiris J Daskalakis Journal: Neuropsychopharmacology Date: 2017-05-29 Impact factor: 7.853
Authors: Tyler S Kaster; Zafiris J Daskalakis; Yoshihiro Noda; Yuliya Knyahnytska; Jonathan Downar; Tarek K Rajji; Yechiel Levkovitz; Abraham Zangen; Meryl A Butters; Benoit H Mulsant; Daniel M Blumberger Journal: Neuropsychopharmacology Date: 2018-06-18 Impact factor: 7.853
Authors: Robin F H Cash; Yoshihiro Noda; Reza Zomorrodi; Natasha Radhu; Faranak Farzan; Tarek K Rajji; Paul B Fitzgerald; Robert Chen; Zafiris J Daskalakis; Daniel M Blumberger Journal: Neuropsychopharmacology Date: 2016-07-27 Impact factor: 7.853
Authors: Xiaoming Du; Laura M Rowland; Ann Summerfelt; Andrea Wijtenburg; Joshua Chiappelli; Krista Wisner; Peter Kochunov; Fow-Sen Choa; L Elliot Hong Journal: Brain Stimul Date: 2018-05-04 Impact factor: 8.955